U.S. patent number 4,407,960 [Application Number 06/162,811] was granted by the patent office on 1983-10-04 for visual chemical indicating composition for monitoring sterilization.
This patent grant is currently assigned to American Sterilizer Company. Invention is credited to Joseph P. Tratnyek.
United States Patent |
4,407,960 |
Tratnyek |
October 4, 1983 |
**Please see images for:
( Certificate of Correction ) ** |
Visual chemical indicating composition for monitoring
sterilization
Abstract
An indicator system and device for visually monitoring ethylene
oxide sterilization by color changes of the indicating composition
of the system upon sufficient and properly conditioned exposure of
the composition to ethylene oxide provides a controlled method for
indicating the effective sterilization of articles by ethylene
oxide. The indicating composition of this invention undergoes color
changes that are progressive with the conditions and periods of
sterilization, such that a final and complete color change
indicates the completion of an effective ethylene oxide
sterilization. The indicating composition comprises a leuco
precursor of an aryl methane dye selected from the groups herein
defined; and an acidic constituent. Acidic organic compounds such
as diphenolic acid (4,4-bis [4-hydroxyphenyl] pentanoic acid) are
effective acid constituents because they enhance hue, develop color
and stabilize the final color change. The indicating composition is
integrated into an indicator system and device further comprising a
substrate or carrier and polymeric binder, any one or more of which
may also provide wholly or in part the acidic constituent of the
indicating composition. The indicator device in the form of a
coated ticket or tape is disposed with the articles to be
sterilized within an ethylene oxide sterilization chamber. Contact
with ethylene oxide is maintained until a final color change,
usually from a definite color to substantially colorless, occurs in
the indicator, signifying the completion of an effective ethylene
oxide sterilization of the articles.
Inventors: |
Tratnyek; Joseph P. (Sudbury,
MA) |
Assignee: |
American Sterilizer Company
(Erie, PA)
|
Family
ID: |
22587227 |
Appl.
No.: |
06/162,811 |
Filed: |
June 25, 1980 |
Current U.S.
Class: |
436/1; 116/207;
374/162; 436/2; 436/127; 116/206; 252/408.1; 436/93; 422/404 |
Current CPC
Class: |
A61L
2/28 (20130101); G01N 31/226 (20130101); A61L
2/206 (20130101); Y10T 436/142222 (20150115); Y10T
436/20 (20150115) |
Current International
Class: |
A61L
2/28 (20060101); A61L 2/26 (20060101); G01N
31/22 (20060101); G01N 021/06 (); C09K
003/34 () |
Field of
Search: |
;252/408,408.1
;116/206,207 ;73/356 ;23/23R,23D ;422/56,57,55 ;436/1,2,93,127
;374/161,162 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
50-40475 |
|
Apr 1975 |
|
JP |
|
1405701 |
|
Sep 1975 |
|
GB |
|
Primary Examiner: Gron; Teddy S.
Attorney, Agent or Firm: Yeager; Robert D.
Claims
What is claimed is:
1. A chemical indicating composition for visually monitoring
ethylene oxide sterilization comprising:
the reaction product of (i) at least one indicator compound
selected from the group consisting of Michler's hydrol, crystal
violet lactone, malachite green leuco and crystal violet leuco and
(ii) an acidic material selected from the group consisting of
acid-earths and diphenolic acids; said reaction product being in
the presence of ethylene oxide.
2. A chemical indicating composition as recited in claim 1
wherein:
said reaction product is deposited upon a substrate.
3. A chemical indicating composition as recited in claim 2
wherein:
said substrate has a pH range of 3.3 to 5.8.
4. A chemical indicating composition as recited in claim 1
wherein:
said reaction product is contained in a polymeric binder that is
permeable at a finite rate to ethylene oxide.
5. A chemical indicating composition as recited in claim 1
wherein:
said indicator compound is Michler's hydrol.
6. A chemical indicating composition as recited in claim 1
wherein:
said indicator compound is malachite green leuco.
7. A chemical indicating composition as recited in claim 6
wherein:
said acidic material has a pH range of 3.3 to 5.8.
8. A chemical indicating composition as recited in claim 1
wherein:
said acidic material is 4,4-bis(4hydroxyphenol)pentanoic acid.
9. A chemical indicating composition as recited in claim 1
wherein:
said indicator compound is Michler's hydrol and said acidic
material is 4,4-bis(4hydroxyphenol)pentanoic acid in concentration
greater than that of the Michler's hydrol.
10. A chemical indicating composition for visually monitoring
ethylene oxide sterilization comprising:
at least one indicator compound selected from the group consisting
of Michler's hydrol, crystal violet lactone, malachite green leuco
and crystal violet leuco; and 4,4-bis(4hydroxyphenol)pentanoic
acid.
11. A method for visually monitoring ethylene oxide sterilization
comprising the steps of:
introducting into a sterilization chamber the reaction product
of
(i) at least one indicator compound selected from the group
consisting of Michler's hydrol, crystal violet lactone, malachite
green leuco and crystal violet leuco, and
(ii) an acidic material selected from the group consisting of
acid-earths and diphenolic acids;
contacting said reaction product with ethylene oxide; and observing
the presence or absence of an irreversible color change in said
reaction product.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to color changing compositions and devices
that visually monitor a sterilization cycle.
2. Description of the Prior Art
Devices that contain chemical compositions that will change color
when exposed to alkylating sterilants, such as ethylene oxide,
under sterilization conditions are known as sterilization
indicators. They are one means of monitoring the effectiveness of a
sterilization process such as those cycles used in hospitals for
sterilizing glassware, medical instruments and wrapped goods.
Indicators are placed within the sterilization chamber inside or
with the goods to be sterilized (load).
Color changes occur because of the reaction between the chemical
ingredients in the indicator and the alkylating sterilant (i.e.
ethylene oxide). The indicator is further designed so that the
reaction will take place at the particular ethylene oxide
concentration, moisture and temperature, that is required to
achieve sterility in the load. It may also be adjusted to the time
period of the particular sterilization cycle if this is
desired.
It is therefore not adequate for an indicator just to change color
when exposed to ethylene oxide; it must respond in an integrated
manner to all of the parameters encountered in a sterilization
cycle, specifically time, temperature, pressure, humidity and
concentration of sterilant.
A popular means of monitoring ethylene oxide sterilization relies
on detecting visually a pH change within an indicator; the pH
changes are produced when ethylene oxide reacts with the specified
chemical of the indicator in the presence of a pH sensitive
dyestuff.
Other means of monitoring ethylene oxide sterilization depend on
alkylation of a specified chemical by ethylene oxide to produce a
color compound.
Some of the known chemicals utilized in indicators are substituted
pyridines and isoquinolines, halide salts of metals, magnesium
chloride, 4,4'(nitro-benzyl)pyridine, and triphenylmethanes.
Problems associated with prior indicators include:
(1) Weak or ambiguous color changes,
(2) Use of heavy metal salts or other toxic ingredients,
and
(3) Measuring an induced change, such as pH rather than a direct
sterilization effect of ethylene oxide.
Triphenylmethane dyes are part of a large, well-known group of
commercially available organic synthetic dyes called the
triarylmethane dyes. Triarylmethane dyes are derivatives of
triphenylmethane (C.sub.6 H.sub.5).sub.3 CH and
diphenylnaphthylmethane (C.sub.6 H.sub.5).sub.2 CH(C.sub.10
H.sub.7) to which auxochromic and bathochromic (color producing)
groups like amino (NH.sub.2) and hydroxyl (OH) have been added. A
triarylmethane dye is formed in substantially the following stages:
formation of a colorless leuco base; conversion of the leuco base
to the colorless carbinol or color base, and finally formation of
the triarylmethane dye (which is a resonance hybrid radical-ion) by
treatment (oxidation) with acid.
In the aldehyde method of preparation of triarylmethane dyes, an
aromatic aldehyde provides the central carbon atom of the dye
radical. Two moles of an aromatic amine are condensed with an
aromatic aldehyde to yield the leuco base. The leuco base is
oxidized to the carbinol base, which, in the presence of acid, is
converted to the dye.
In a hydrol synthesis, the central carbon atom is supplied by a
substituted benzhydrol, such as Michler's hydrol.
Thus a leuco base form and Michler's hydrol (which is termed an
intermediate in a dye synthesis) are precursors in the formation of
triarylmethane dyes. With the exception of the leuco base, crystal
violet lactone, which has been used in the production of a new kind
of carbonless copy paper, these precursors have not obtained end
uses.
SUMMARY OF THE INVENTION
In the chemical indicating composition and device of this
invention, it has been found that the dye-synthesis intermediate,
Michler's hydrol, and the leuco bases can themselves be utilized,
in the presence of acid, as visual indicating compositions for
sterilization by an alkylating agent, such as sterilization by
ethylene oxide.
The new indicating composition and system employing said
composition of this invention monitors sterilization by ethylene
oxide by chemical reactions of the composition with ethylene oxide
that cause a visually perceptible color change from color to
colorless. The color is unambiguous and irreversible. The
composition is non-toxic to human beings, and the chemical reaction
does not rely on an induced pH change.
The indicating composition of this invention comprises a selected
precursor or analog thereof of a triarylmethane dye, and an acidic
constituent. The precursor and acidic constituent react to produce
a color (e.g. blue) which upon exposure to ethylene oxide under
sterilization conditions will change to essentially colorless.
Triarylmethane precursors effective for use as color change
indicators herein are selected from the leuco base forms and
dye-synthesis intermediates, and include: Michler's hydrol
(4,4'-bis[dimethylamino]benzhydrol), Michler's hydrol
leucobenzotriazole, Michler's hydrol leucomorpholine, Michler's
hydrol leucobenzenesulfonamide, malachite green leuco, rhodamine
lactam, crystal violet lactone, and crystal violet leuco.
The acidic conjugate compound functions to develop color, enhance
hue, and stabilize the final color change. Acidic organic
constituents such as the diphenolic acids are preferred, however,
clay materials (or acid-earth materials) such as those found in
paper substrates and acid-acting solvents, such as certain
alcohols, will also provide an effective acidic environment.
The indicating composition is formed into an indicator system (or
device) by the addition of a polymer which functions to regulate
the permeability of the system to moisture and gas concentration,
and thereby regulate the reaction rate. The polymer may also
function as an adhesive for the composition. The system may be
conveniently disposed on any inert receptive material or substrate
such as cellulose blotter or silica gel.
The system, comprising triarylmethane precursor, acidic
constituent, substrate (carrier) and polymer (polymeric binder) is
disposed in the form of a coated ticket or tape in a sterilization
chamber with the load to be sterilized. Sterilization by ethylene
oxide is insured when a final color change to colorless occurs in
the indicator.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Structurally, the triarylmethane dye is an ionic compound with the
chromophore, or color producing portion of the molecule, being a
positive radical ion. This radical ion is actually a resonance
hybrid, that is, it has a delocalized positive charge on the
portion of the molecule. Resonance is considered the property of
the molecule that is color producing. The triarylmethane dye may
thus also be referred to as the dye radical or dye radical ion with
reference to this color producing molecular structure.
The precursor leuco base-forms and the benzhydrol intermediates,
(such as Michler's hydrol) from which the dye radical is derived,
are non-resonating forms and therefore non-color producing. A leuco
base precursor has a central saturated carbon atom, as does the
intermediate, Michler's hydrol. The precursors herein used may be
considered to be alkylated precursors of the triarylmethane dyes.
The selected groups of leuco base and intermediates (also herein
referred to as precursors) chosen for use in the indicating
composition of the present invention include:
(i) Michler's hydrol,
(ii) Michler's hydrol leucomorpholine,
(iii) Michler's hydrol leucobenzotriazole,
(iv) Michler's hydrol leucobenzenesulfonamide,
(v) Malachite green leuco,
(vi) Rhodamine lactam,
(vii) Crystal violet leuco, and
(viii) Crystal violet lactone: all of which fall within the group
identified structurally as: ##STR1## wherein x is selected from the
group consisting of:
and R is selected from the group consisting of: ##STR2## and R' is
selected from the group consisting of: ##STR3##
These colorless forms of the triarylmethane dye precursors require
the presence of an acidic constituent to develop color. The exact
chemical mechanism is unknown, but it is believed to involve attack
at reactive sites in the leuco or intermediate molecule, resulting
in a resonance hybrid with visible color. It is significant that
the color producing resonance hybrid radical of this reaction
cannot be used to resynthesize the original leuco or intermediate
form in a reverse reaction. Thus the radical ion herein formed is
not the radical ion of the known triarylmethane dyes. The color
radical formed herein will undergo further reaction with an
alkylating agent, such as ethylene oxide, to produce a final form
which is again colorless. However again the final colorless
composition or chemical cannot be hydrolized to the dye form
reactant. The theoretical mechanism of the reaction of the chemical
composition of the present invention is thus:
a known leuco base/intermediate is acidified to produce a colored
unidentified dye-radical which in turn yields in the presence of
ethylene oxide an unknown colorless form.
These leuco bases and intermediates are shown herein to be highly
useful as ethylene oxide indicators, because the color formation is
clear, unambiguous and stable; and a sharp colorless end point is
reached when they react with ethylene oxide under sterilization
conditions.
Because the leuco base forms and intermediates (precursors) are
essentially available as crystalline solids, a solvent is required
in their preparation for use as indicators. This solvent is used to
dispose the precursors in solution on the substrate. It is critical
that the solvent employed be essentially inert, or in any event not
inhibitory of the color development. The solvent may contribute to
the acidity environment or itself form the acid environment, as for
example certain alcohols which may react as Lewis acids. It will
also be appreciated that excess acidity can adversely affect color
formation by reason of the reactive sites of the leuco bases and
intermediates. This is especially the case for example with the use
of Michler's hydrol, which has a highly reactive hydroxyl group and
is therefore especially vulnerable to oxidative degradation.
Acetone and methanol were the solvents of choice for applying the
color active coating in the tests herein; choice of solvent is
however variable within the above limitations.
Conditions applicable to choice of a solvent similarly apply to a
choice of substrate or carrier material upon which the indicating
composition is to be disposed. An inert carrier material may be
utilized; or any acid-earth or clay material (such as found in
paper), may be used which will cooperatively or independently
function as the acidic constituent. Commercially available treated
substrates such as polyester film having a surface of silica gel
(pH 4-7.0) or cellulose blotters (pH 2-4.9) were predominately used
as substrates herein.
As described above, the aforesaid substrates and solvents may
function as the acidic constituent of the indicating composition of
the present invention. However it was found that the use of the
diphenolic acid, 4,4-bis(4hydroxyphenyl)pentanoic acid, which is
used in the preferred embodiment, is particularly effective as an
acidic organic additive which develops color, stabilizes color and
enhances hue.
The acid constituent of the present invention is in effect that
which produces an environment for the reaction of the precursor
chemical. This acid environment may be produced by (i) an acidic
substrate such as acid-earth or clay with the addition of
4,4-bis(4hydroxyphenyl)pentanoic acid, such substrates having a pH
range of 3.3 to 5.8; (ii) an originally neutral to slightly
alkaline substrate (pH 7.0-7.5) that by acid-base
ionization-reaction with a solvent becomes weakly acidic; (iii) an
acidic substrate alone (the aforedescribed clays or acid-earths);
or (iv) the solvent-substrate of (ii) with the addition of
4,4-bis(4hydroxyphenyl)pentanoic acid. In this acidic environment,
produced by the reaction of substrate, solvent and/or acid, the
colorless leuco precursors undergo bond-breaking resulting in the
aforedescribed resonance which thereby produces color upon the
surface of the substrate. When this is subsequently exposed to
ethylene oxide under sterilization conditions as more specifically
described below, the color changes to essentially colorless,
indicating completion of a sterilization cycle. Because an
indicating compound, composition system or device must be
responsive to the total sterilization conditions of ethylene oxide,
rather than the mere presence of ethylene oxide, all test data are
derived from experiments carried out under suitable sterilization
conditions which are defined in part by the following
parameters:
______________________________________ Time: 1-3 hours Temperature:
67.degree.-140.degree. F. Pressure: 8-10 psig. Relative humidity:
30-100% Ethylene oxide concentration in air: 300-1200 mg/liter
______________________________________
The term "exposure to ethylene oxide" is used herein to designate
exposure to ethylene oxide under sterilization conditions.
The following specific sterilization conditions are standard for
the experiments hereinafter described:
______________________________________ Time: 1.5 hours Temperature:
140.degree. F. Pressure: 8-10 psig. Chamber: AMSCO Portagas Unit
______________________________________
The precursor chemical was applied to the substrate from a solvent
solution by saturating the substrate with about 5 drops of solution
followed by air drying. The so-prepared test strips were then
exposed to ethylene oxide, and observations of color and color
changes were made. "Final" color as indicated in TABLE I designates
color observed after several months of aging. Aging was utilized to
determine the stability of color. Substrates are headed "Treated
substrates" in reference to their specific function as indicator
substrates which are commercially available, and the pH of the
substrate is given in most instances because of its relevance to
the acid reaction environment as discussed above.
In these specific examples, concentration of the precursor
chemicals was in the range of 0.1-1.0 percent by weight of the
solvent. Where 4,4-bis(4-hydroxyphenyl)pentanoic acid was also
added, the concentration of this acid was also in the range of
0.1-1.0 percent by weight of the solvent. Within this range,
relative concentrations of the precursor and the acid did not
materially affect the results.
The selected precursor compounds will produce color and color
changes within broad parameters of an acidic environment that can
be created either by the action or interaction of a solvent and a
substrate, the substrate alone, or an acid additive. However,
preferred reliability is achieved by their use as indicators within
selected parameters of compounds and conditions shown to provide
color and color changing results that are consistent, stable, and
clearly defined. Therefore, the class of indicating compounds of
this invention is further subdivided into sub-classes on the basis
of respective conditions of preferred reliability. Details and
examples are given below.
It will be apparent to those skilled in the art that quantitative
as well as qualitative modifications of components within the
composition and system will vary the color and color changing
effects, as will the sterilization conditions under which they are
practiced.
LEUCO CHEMICALS IN NON-ACID ENVIRONMENT
Referring now to Table I, leuco precursor chemicals, such as
Michler's hydrol leucobenzenesulfonamide and Crystal Violet lactone
(Test Nos. 1 and 2) do not undergo color change in a non-acid
environment. In these examples, untreated filter paper was employed
as a substrate and no 4,4-bis(4hydroxyphenyl)pentanoic acid was
added. Therefore, the reaction environment was essentially neutral,
and the criticality of acidity to color formation was
demonstrated.
TABLE I
__________________________________________________________________________
COLOR CHANGES WITH COLOR CHANGES ETHYLENE OXIDE AFTER CHEMICAL
TREATED WITH ETHYLENE OXIDE ADDITION OF DIPHENOLIC ACID SOLVENT
SUBSTRATE BEFORE AFTER FINAL BEFORE AFTER FINAL
__________________________________________________________________________
Michler's hydrol Filter Paper NONE NO TESTS leucobenzenesulfonamide
RUN Acetone Crystal Violet lactone Filter Paper NONE NO TESTS
Acetone RUN Michler's hydrol Silica gel lt. blue yellowish
colorless intense blue lt. blue gray- Acetone (pH 7.4-7.5)
colorless Cellulose blotter NONE intense blue lt. blue stable (pH
4.2-4.9) pale blue Polyamide NONE NO TESTS (pH 4.6-5.0) RUN Silica
gel B brt. blue dull brown yellowish NO TESTS (pH 4.8) RUN
Cellulose PEI NONE NO TESTS (pH 2.9-3.2) RUN Cellulose DEAE
green/blue dull brown yellowish NO TESTS (pH 3.3-3.7) RUN Cellulose
B green/blue dull brown yellowish NO TESTS (pH 4.8-5.4) RUN
Aluminum Oxide olive dull brown yellowish NO TESTS (pH 5.2-5.7) RUN
Michler's hydrol Silica gel lt. blue yellowish colorless intense
blue lt. blue colorless Ethanol (pH 7.4-7.5) Cellulose blotter blue
yellowish colorless intense blue lt. blue stable (pH 4.2-4.9) pale
blue Michler's hydrol Silica gel NONE Ethanol (7.4-7.5) (in varying
percents Cellulose blotter NONE deep blue lt. blue of Michler's
hydrol) (4.2-4.9) (Color only when % DPA is greater than %
Michler's Hydrol) Michler's hydrol Silica gel NONE leucomorpholine
(7.4-7.5) Acetone or Ethanol Cellulose blotter NONE (4.2-4.9) brt.
blue light blue Michler's hydrol Silica gel NONE NONE
leucobenzenesulfonamide (7.4-7.5) Acetone or Ethanol Cellulose
blotter NONE brt. blue light almost (4.2-4.9) colorless Michler's
hydrol Silica gel NONE NONE benzetriazole (7.4-7.5) Acetone or
Ethanol Cellulose blotter NONE brt. blue pale blue (4.2-4.9)
Crystal violet Silica gel brt. purple pale violet pale gray/
intense almost lactone (7.4-7.5) purple purple colorless Acetone or
Ethanol Cellulose blotter NONE deep blue light blue (4.2-4.9) 10.
Crystal violet Silica gel brt. purple pale blue intense almost
leuco (7.4-7.5) violet colorless Acetone or Ethanol Cellulose
blotter NONE deep blue pale blue (4.2-4.9) Rhodamine lactam Silica
gel light pink colorless bright pink very pale pink Acetone
(7.4-7.5) Cellulose blotter NONE (4.2-4.9) Malachite Silica gel
blue pale blue colorless NONE green leuco (7.4-7.5) Acetone or
Ethanol Cellulose blotter green/blue pale blue colorless NONE
(4.2-4.9)
__________________________________________________________________________
MICHLER's HYDROL
Michler's Hydrol (4,4'-bis(dimethylamino)benzhydrol)
The composition consisting of the triphenylmethane dye
intermediate, Michler's hydrol, and the acidic constituent,
4,4-bis(4hydroxyphenyl)pentanoic acid, is an excellent indicator
for ethylene oxide sterilization, because as shown in Tests 3 and 4
of Table I, intense blue colors are formed which react with
ethylene oxide to a precise, uniform, colorless and stable end
point.
Also shown in Tests 3 and 4, Michler's hydrol on the paper (i.e.
clay) substrates produce generally blue colors which change
essentially colorless, (yellowish). While effective color change
occured with the use of Michler's hydrol alone, the addition of
4,4-bis(4hydroxyphenyl)pentanoic acid produced more intense
colors.
Acetone, methanol, were solvents used to apply the composition to
the substrates. As seen in Test No. 5 of Table I, the solvent
ethanol produced color only when the percent (by weight of solvent)
of 4,4-bis(4hydroxyphenyl)pentanoic acid ("DPA" in the table) was
greater than the percent (by weight of solvent) of Michler's
hydrol.
In Test Nos. 3 and 4 of Table I, the concentrations of Michler's
hydrol and 4,4-bis(4hydroxyphenyl)pentanoic acid were in the range
of 0.1 to 0.5 percent by weight of the solvent. Within this range
their relative concentration did not materially affect the color
results. For percentage concentrations greater than 0.1 to 0.5
percent, the best relative concentrations of these components was
determined to be in ratios in the range of 0.1-10 grams acid:
0.1-10 grams hydrol. At these proportions the color change is found
to be from distinct colors of dark blue or blue-green to strongly
contrasting pale blue or colorless. The most stable and intense
blue colors are produced with high concentrations of
4,4-bis(4hydroxyphenyl)pentanoic acid relative to the Michler's
hydrol. However, higher concentrations of Michler's hydrol (e.g.
10:1) also cause more saturated color.
MICHLER'S HYDROL LEUCOMORPHOLINE
Michler's Hydrol Leucobenzenesulfonamide
Michler's Hydrol Benzetriazole
The compounds of this subclass of precursor chemicals have the
following structural formulas: ##STR4##
Michler's hydrol leucomorpholine ##STR5##
Michler's hydrol leucobenzenesulfonamide ##STR6##
Michler's hydrol leucobenzotriazole
Michler's hydrol leucomorpholine, Michler's hydrol
leucobenzenesulfonamide, and Michler's hydrol benzotriazole are
leuco base precursors of the triarylmethane dyes which are
derivatives of Michler's hydrol.
As shown on Table I, Test Nos. 5, 6, 7 and 8, these compounds also
obtained preferred reliability with the addition of
4,4-bis(4hydroxyphenyl)acid. The operable relative concentration
parameters of the leucochemical and
4,4-bis(4hydroxyphenyl)pentanoic acid were again in the range of
0.1 to 0.5 percent by weight of solvent; within this range relative
concentrations of leucochemical to acid did not materially affect
the color results. As shown in Table I, Test Nos. 6, 7 and 8;
4,4-bis(4hydroxyphenyl)pentanoic acid used with Michler's hydrol
leucomorpholine, Michler's hydrol leucobenzenesulfonamide and
Michler's hydrol benzetriazole in acetone or ethanol solvents
produced bright blue colors which upon exposure to ethylene oxide
faded to essentially colorless.
CRYSTAL VIOLET LACTONE
Crystal Violet Leuco
The leuco bases, crystal violet lactone and crystal violet leuco
have the structural formulas: ##STR7##
As shown in Test Nos. 9 and 10 of Table I, these compounds produced
strong purple hues in an acid environment which faded to pale
colors on exposure to ethylene oxide. The addition of
4,4-bis(4hydroxyphenyl)pentanoic acid again intensified color
effects achieved with substrate or substrate-solvent alone.
RHODAMINE LACTAM
The leuco chemical, rhodamine lactam has the structural formula:
##STR8##
Rhodamine lactam produced pink hues which upon exposure to ethylene
oxide faded to colorless. Again the addition of
4,4-bis(4hydroxyphenyl)pentanoic acid was effective in intensifying
color and stabilizing color such that fading would not take place
independently (without the ethylene oxide exposure). Preferred
results where rhodamine lactam was used as an indicator were found
to occur in an acid environment produced by an acid-earth substrate
with acetone solvent, and the addition of
4,4-bis(4hydroxyphenyl)pentanoic acid. (Table I, Test No. 11).
MALACHITE GREEN LEUCO
Malachite green leuco has the structural formula: ##STR9##
As shown in Table I, Test No. 12, malachite green leuco produced
distinct blue to green-blue color in an acid environment achieved
by substrate and/or substrate-solvent. The addition of
4,4-bis(4hydroxyphenyl)pentanoic acid under conditions of these
tests was shown to inhibit color formation. The most constant and
pronounced color change when using malachite green leuco as an
indicator occured with the use of acetone or ethanol as the
applicator solvent, and on an acid environment of clay substrate
and/or substrate-solvent alone.
The aforedescribed triarylmethane dye precursors comprising the
leuco base forms and Michler's hydrol intermediates have been shown
to be effective for use as visual chemical indicators for ethylene
oxide within the parameters and conditions set forth above. It is
reasonable to conclude that analogs of the Michler's hydrol
intermediates such as ethyl hydrol will react substantially the
same as the methyl hydrol (Michler's). A unique end use has thus
been presented for these precursors which in the presence of acid
are applied as visual chemical indicating compositions for
alkalylating agents such as ethylene oxide.
While the aforedescribed precursors were color producing, similar
compounds tested were not effective even with the addition of
4,4-bis(4hydroxyphenyl)pentanoic acid. For example,
triphenylmethane, triphenylamine, Michler's ketone,
2-nitrodiphenolamine, aurintricarboxylic acid and leucamine did not
produce color or change color under any of the conditions herein
utilized.
INDICATOR SYSTEM
The indicator system of this invention is achieved by integrating
the indicating composition of this invention with a polymeric
binder which, when applied to a substrate or carrier, forms a
coated ticket or tape device.
The polymer coating obtains a desired response in the sterilization
cycle. Properties of the chosen polymer, for example permeability
to moisture and ethylene oxide are adjusted to regulate the rate of
the reaction between the indicating composition and ethylene
oxide.
The ticket or tape indicator system is disposed in a sterilizer
chamber. The system functions in a chamber as an integrator for
sterilization, in that when the colorless end point is reached in
the indicating composition (thereby in the ticket or tape) the
conditions for sterilization have been achieved in the chamber. The
system (i.e. the reaction rate) may be adjusted to suitable
predetermined sterilization conditions, such as time, humidity or
concentration of ethylene oxide.
Preferred embodiments of the indicator system are those indicator
compositions comprising Michler's hydrol and the acidic
constituents shown in Table II. Compositions of the indicator
system are set forth in grams of materials used. Systems 1 and 2,
in Table II use alcohol soluble nylon as a polymeric binder with
the solvent methanol, 4,4-bis(4hydroxyphenyl)pentanoic acid, and
Michler's hydrol on substrates (clay containing paper) in the pH
range of 4.1-6.3. In system 2, styrene-maleic anhydride resin is
utilized as the organic acid constituent. This provides an
indicator system that changes from a dark blue to colorless on
sterilization by ethylene oxide. Systems 3 and 4 of Table II
utilize ethyl cellulose as the polymeric binder. System 3 comprises
ethyl cellulose, acetone as a solvent with
4,4-bis(4hydroxyphenyl)pentanoic acid and Michler's hydrol. System
4 comprises ethyl cellulose, methylene chloride and acetone as
solvents 4,4-bis(4hydroxyphenyl)pentanoic acid, silica as an acidic
binder modifier and Michler's hydrol.
It is noted that in the systems herein set forth the solvent, which
although significant as discussed in the reactions above, is used
in the initial application of the composition to the substrate and
subsequently evaporates. Thus it is not an integral component of
the indicator system. The use of silica as an acidic binder
modifier is essentially another means by which acid-earth or clay
is introduced into the system.
TABLE II ______________________________________ INDICATOR SYSTEMS 1
2 3 4 ______________________________________ Alcohol soluble nylon
2g 2g Ethyl Cellulose 5g 2g Styrene-maleic anhydride resin 1.0g
Silica 5.0g 5.0g 4,4-bis (4 hydroxyphenyl) 1.0g 1.0g 1.0g pentanoic
acid Michler's hydrol 0.05g 0.05g 0.05g 0.05g Methanol 48g 48g 9g
Acetone 36g 10g Methylene chloride 38g Clay-containing Coated
boxboard: (pH 4.1-4.7) Substrates Coated paper cover stock: (pH
4.7-4.9) Shiny coated paper stock: (pH 5.7-6.3)
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